Infertility as a Contemporary Social and Therapeutic Challenge - A Literature Review
DOI:
https://doi.org/10.12775/JEHS.2025.86.67351Keywords
infertility, endometrosis, immunological infertility, PCOS, testicular cancerAbstract
INTRODUCTION: Infertility is a multifactorial condition affecting both women and men, with substantial social, psychological, and medical implications. It arises from hormonal, anatomical, genetic, infectious, and lifestyle-related factors.
AIM OF STUDY: This review aims to summarize current knowledge on the etiology, pathophysiology, and therapeutic approaches to infertility in both sexes, emphasizing major conditions.
MATERIAL AND METHODS: A literature review was conducted analyzing peer-reviewed studies on reproductive health from PubMed and GoogleScholar. Both male and female infertility were considered, focusing on factors influencing gametogenesis, fertilization, embryo implantation and pregnancy outcomes.
BASIC RESULTS: In women, infertility is influenced by endometriosis, which alters implantation through inflammatory and immunomodulatory mechanisms; PCOS, which disrupts hormonal balance and ovulation; and uterine fibroids, which impair myometrial contractility and endometrial receptivity. In men, infertility results from genetic and acquired causes, including azoospermia, varicocele, infections, and malignancies, with oxidative stress, antisperm antibodies, and dysbiosis contributing to impaired spermatogenesis and sperm transport. Lifestyle interventions, as well as surgical and pharmacological treatments, can improve reproductive outcomes.
CONCLUSION: Infertility is a complex, interrelated condition requiring multidisciplinary management. Understanding biological, genetic, immunological and lifestyle factors is essential to optimize therapy, enhance conception, and increase live birth rates. Targeting modifiable factors such as diet, physical activity, and body weight is a promising adjunct to conventional treatment.
References
[1] Krzysztof Łukaszuk, Katarzyna Kozioł, Grzegorz Jakiel, Artur Jakimiuk i Piotr Jędrzejczak. „Diagnostyka i leczenie niepłodności — rekomendacje Polskiego Towarzystwa Medycyny Rozrodu i Embriologii (PTMRiE) oraz Polskiego Towarzystwa Ginekologów i Położników (PTGP).” Via Medica, 31 10 2018: 112-140.
[2] Erika Kelley i Sheryl Kingsberg . „Sexuality and Infertility.” Obstetrics and Gynecology Clinics of North America, June 2024, wyd. 2: 31
[3] Johnson NP, Hummelshoj L, Adamson GD, et al. World Endometriosis Society consensus on the classification of endometriosis. Hum Reprod. 2017;32(2):315-324. doi:10.1093/humrep/dew293
[4] Creating Solutions in Endometriosis: Global Collaboration through the World Endometriosis Research Foundation January 2010 Journal of Endometriosis 2(1):3-6, DOI:10.1177/228402651000200102
[5] Steele RW, Dmowski WP, Marmer DJ. Immunologic aspects of human endometriosis. Am J Reprod Immunol (1980). 1984;6(1):33-36. doi:10.1111/j.1600-0897.1984.tb00106.x
[6] Dietrich JE, Millar DM, Quint EH. Obstructive reproductive tract anomalies. J Pediatr Adolesc Gynecol. 2014;27(6):396-402. doi:10.1016/j.jpag.2014.09.001
[7] Du H, Taylor HS. Contribution of bone marrow-derived stem cells to endometrium and endometriosis. Stem Cells. 2007;25(8):2082-2086. doi:10.1634/stemcells.2006-0828
[8] Simpson JL, Elias S, Malinak LR, Buttram VC Jr. Heritable aspects of endometriosis. I. Genetic studies. Am J Obstet Gynecol. 1980;137(3):327-331. doi:10.1016/0002-9378(80)90917-5
[9] Taylor HS, Bagot C, Kardana A, Olive D, Arici A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328-1331. doi:10.1093/humrep/14.5.1328
[10] Zanatta A, Rocha AM, Carvalho FM, et al. The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: a review. J Assist Reprod Genet. 2010;27(12):701-710. doi:10.1007/s10815-010-9471-y
[11] Lessey BA, Ilesanmi AO, Castelbaum AJ, et al. Characterization of the functional progesterone receptor in an endometrial adenocarcinoma cell line (Ishikawa): progesterone-induced expression of the alpha1 integrin. J Steroid Biochem Mol Biol. 1996;59(1):31-39. doi:10.1016/s0960-0760(96)00103-3
[12] Susheelamma CJ, Pillai SM, Asha Nair S. Oestrogen, progesterone and stem cells: the discordant trio in endometriosis?. Expert Rev Mol Med. 2018;20:e2. Published 2018 Mar 8. doi:10.1017/erm.2017.13
[13] Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535-549. doi:10.1016/j.ogc.2012.10.002
[14] Ozkan S, Murk W, Arici A. Endometriosis and infertility: epidemiology and evidence-based treatments. Ann N Y Acad Sci. 2008;1127:92-100. doi:10.1196/annals.1434.007
[15] Holoch KJ, Lessey BA. Endometriosis and infertility. Clin Obstet Gynecol. 2010;53(2):429-438. doi:10.1097/GRF.0b013e3181db7d71
[16] Oral E, Arici A, Olive DL, Huszar G. Peritoneal fluid from women with moderate or severe endometriosis inhibits sperm motility: the role of seminal fluid components. Fertil Steril. 1996;66(5):787-792. doi:10.1016/s0015-0282(16)58637-3
[17] Hodgson RM, Lee HL, Wang R, Mol BW, Johnson N. Interventions for endometriosis-related infertility: a systematic review and network meta-analysis. Fertil Steril. 2020;113(2):374-382.e2. doi:10.1016/j.fertnstert.2019.09.031
[18] Capezzuoli T, Rossi M, La Torre F, Vannuccini S, Petraglia F. Hormonal drugs for the treatment of endometriosis. Curr Opin Pharmacol. 2022;67:102311. doi:10.1016/j.coph.2022.102311
[19] de Souza Pinto LP, Ferrari G, Dos Santos IK, de Mello Roesler CR, de Mello Gindri I. Evaluation of safety and effectiveness of gestrinone in the treatment of endometriosis: a systematic review and meta-analysis. Arch Gynecol Obstet. 2023;307(1):21-37. doi:10.1007/s00404-022-06846-0
[20] Fruzzetti F, Perini D, Russo M, Bucci F, Gadducci A. Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2017;33(1):39-42. doi:10.1080/09513590.2016.1236078
[21] Patten RK, McIlvenna LC, Moreno-Asso A, et al. Efficacy of high-intensity interval training for improving mental health and health-related quality of life in women with polycystic ovary syndrome. Sci Rep. 2023;13(1):3025. Published 2023 Feb 21. doi:10.1038/s41598-023-29503-1
[22] Legro RS, Dodson WC, Kris-Etherton PM, et al. Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2015;100(11):4048-4058. doi:10.1210/jc.2015-2778
[23] Donnez J, Taylor HS, Marcellin L, Dolmans MM. Uterine fibroid-related infertility: mechanisms and management. Fertil Steril. 2024;122(1):31-39. doi:10.1016/j.fertnstert.2024.02.049
[24] Somigliana E, Vercellini P, Daguati R, Pasin R, De Giorgi O, Crosignani PG. Fibroids and female reproduction: a critical analysis of the evidence. Hum Reprod Update. 2007;13(5):465-476. doi:10.1093/humupd/dmm013
[25] Casini ML, Rossi F, Agostini R, Unfer V. Effects of the position of fibroids on fertility. Gynecol Endocrinol. 2006;22(2):106-109. doi:10.1080/09513590600604673
[26] Nishino M, Togashi K, Nakai A, et al. Uterine contractions evaluated on cine MR imaging in patients with uterine leiomyomas. Eur J Radiol. 2005;53(1):142-146. doi:10.1016/j.ejrad.2004.01.009
[27] Yoshino O, Hayashi T, Osuga Y, et al. Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids. Hum Reprod. 2010;25(10):2475-2479. doi:10.1093/humrep/deq222
[28] Ikhena DE, Bulun SE. Literature Review on the Role of Uterine Fibroids in Endometrial Function. Reprod Sci. 2018;25(5):635-643. doi:10.1177/1933719117725827
[29] Doherty LF, Taylor HS. Leiomyoma-derived transforming growth factor-β impairs bone morphogenetic protein-2-mediated endometrial receptivity. Fertil Steril. 2015;103(3):845-852. doi:10.1016/j.fertnstert.2014.12.099
[30] Somigliana E, Reschini M, Bonanni V, Busnelli A, Li Piani L, Vercellini P. Fibroids and natural fertility: a systematic review and meta-analysis. Reprod Biomed Online. 2021;43(1):100-110. doi:10.1016/j.rbmo.2021.03.013
[31] Eisenberg ML, Esteves SC, Lamb DJ, et al. Male infertility. Nat Rev Dis Primers. 2023;9(1):49. Published 2023 Sep 14. doi:10.1038/s41572-023-00459-w
[32] Rama N, Lescay H, Raheem O. Male Factor Infertility: What Every OB/GYN Should Know. Obstet Gynecol Clin North Am. 2023;50(4):763-777. doi:10.1016/j.ogc.2023.08.001
[33] Sharma A, Minhas S, Dhillo WS, Jayasena CN. Male infertility due to testicular disorders. J Clin Endocrinol Metab. 2021;106(2):e442-e459. doi:10.1210/clinem/dgaa781
[34] Peña VN, Kohn TP, Herati AS. Genetic mutations contributing to non-obstructive azoospermia. Best Pract Res Clin Endocrinol Metab. 2020;34(6):101479. doi:10.1016/j.beem.2020.101479
[35] Sharma A, Minhas S, Dhillo WS, Jayasena CN. Male infertility due to testicular disorders. J Clin Endocrinol Metab. 2021;106(2):e442-e459. doi:10.1210/clinem/dgaa781
[36] Bryan ER, Kim J, Beagley KW, Carey AJ. Testicular inflammation and infertility: Could chlamydial infections be contributing?. Am J Reprod Immunol. 2020;84(3):e13286. doi:10.1111/aji.13286
[37] Bryan ER, Redgrove KA, Mooney AR, et al. Chronic testicular Chlamydia muridarum infection impairs mouse fertility and offspring development†. Biol Reprod. 2020;102(4):888-901. doi:10.1093/biolre/ioz229
[38] Sucato A, Buttà M, Bosco L, Di Gregorio L, Perino A, Capra G. Human Papillomavirus and Male Infertility: What Do We Know?. Int J Mol Sci. 2023;24(24):17562. Published 2023 Dec 16. doi:10.3390/ijms242417562
[39] Wang Z, Xu X. scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells. Cells. 2020;9(4):920. Published 2020 Apr 9. doi:10.3390/cells9040920
[40] Li H, Xiao X, Zhang J, et al. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine. 2020;28:100604. doi:10.1016/j.eclinm.2020.100604
[41] Kim HH, Goldstein M. Adult varicocele. Curr Opin Urol. 2008;18(6):608-612. doi:10.1097/MOU.0b013e3283136493
[42] Gamidov SI, Ovchinnikov RI, Popova AY, Avakyan AY, Sukhikh GT. Urologiia. 2017;(2 (supplement)):64-72. doi:10.18565/urol.2017.2-supplement.64-72
[43] Fang Y, Su Y, Xu J, et al. Varicocele-Mediated Male Infertility: From the Perspective of Testicular Immunity and Inflammation. Front Immunol. 2021;12:729539. Published 2021 Aug 31. doi:10.3389/fimmu.2021.729539
[44] Zalata A, Hafez T, Van Hoecke MJ, Comhaire F. Evaluation of beta-endorphin and interleukin-6 in seminal plasma of patients with certain andrological diseases. Hum Reprod. 1995;10(12):3161-3165. doi:10.1093/oxfordjournals.humrep.a135879
[45] Sakamoto Y, Ishikawa T, Kondo Y, Yamaguchi K, Fujisawa M. The assessment of oxidative stress in infertile patients with varicocele. BJU Int. 2008;101(12):1547-1552. doi:10.1111/j.1464-410X.2008.07517.x
[46] Moretti E, Cerretani D, Noto D, Signorini C, Iacoponi F, Collodel G. Relationship Between Semen IL-6, IL-33 and Malondialdehyde Generation in Human Seminal Plasma and Spermatozoa. Reprod Sci. 2021;28(8):2136-2143. doi:10.1007/s43032-021-00493-7
[47] Bozhedomov VA, Lipatova NA, Rokhlikov IM, Alexeev RA, Ushakova IV, Sukhikh GT. Male fertility and varicocoele: role of immune factors. Andrology. 2014;2(1):51-58. doi:10.1111/j.2047-2927.2013.00160.x
[48] Wosnitzer MS, Goldstein M. Obstructive azoospermia. Urol Clin North Am. 2014;41(1):83-95. doi:10.1016/j.ucl.2013.08.013
[49] Hubbard L, Rambhatla A, Colpi GM. Differentiation between nonobstructive azoospermia and obstructive azoospermia: then and now. Asian J Androl. 2025;27(3):298-306. doi:10.4103/aja202475
[50] Bieniek JM, Lapin CD, Jarvi KA. Genetics of CFTR and male infertility. Transl Androl Urol. 2021;10(3):1391-1400. doi:10.21037/tau.2020.04.05
[51] Sharma A, Minhas S, Dhillo WS, Jayasena CN. Male infertility due to testicular disorders. J Clin Endocrinol Metab. 2021;106(2):e442-e459. doi:10.1210/clinem/dgaa781
[52] Antony D, Brunner HG, Schmidts M. Ciliary Dyneins and Dynein Related Ciliopathies. Cells. 2021;10(8):1885. Published 2021 Jul 25. doi:10.3390/cells10081885
[53] Inaba K, Mizuno K. Sperm dysfunction and ciliopathy. Reprod Med Biol. 2015;15(2):77-94. Published 2015 Oct 14. doi:10.1007/s12522-015-0225-5
[54] Karnan A, Ledwani A. Barry-Perkins-Young syndrome. Pan Afr Med J. 2024;47:191. Published 2024 Apr 16. doi:10.11604/pamj.2024.47.191.42932
[55] Mohammed SK, Jan A. Young Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 22, 2023.
[56] Sharma A, Minhas S, Dhillo WS, Jayasena CN. Male infertility due to testicular disorders. J Clin Endocrinol Metab. 2021;106(2):e442-e459. doi:10.1210/clinem/dgaa781
[57] Meirow D, Schenker JG. Cancer and male infertility. Hum Reprod. 1995;10(8):2017-2022. doi:10.1093/oxfordjournals.humrep.a136228
[58] Tiwari P, Yadav A, Kaushik M, Dada R. Cancer risk and male Infertility: Unravelling predictive biomarkers and prognostic indicators. Clin Chim Acta. 2024;558:119670. doi:10.1016/j.cca.2024.119670
[59] Minhas S, Bettocchi C, Boeri L, et al. European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility. Eur Urol. 2021;80(5):603-620. doi:10.1016/j.eururo.2021.08.014
[60] Hanson BM, Eisenberg ML, Hotaling JM. Male infertility: a biomarker of individual and familial cancer risk. Fertil Steril. 2018;109(1):6-19. doi:10.1016/j.fertnstert.2017.11.005
[61] Petersen PM, Skakkebaek NE, Vistisen K, Rørth M, Giwercman A. Semen quality and reproductive hormones before orchiectomy in men with testicular cancer. J Clin Oncol. 1999;17(3):941-947. doi:10.1200/JCO.1999.17.3.941
[62] Daum H, Zlotogora J. Fanconi Anemia Gene Variants in Patients with Gonadal Dysfunction. Reprod Sci. 2022;29(5):1408-1413. doi:10.1007/s43032-021-00582-7
[63] Bozhedomov VA, Lipatova NA, Rokhlikov IM, Alexeev RA, Ushakova IV, Sukhikh GT. Male fertility and varicocoele: role of immune factors. Andrology. 2014;2(1):51-58. doi:10.1111/j.2047-2927.2013.00160.x
[64] Golomb J, Vardinon N, Homonnai ZT, Braf Z, Yust I. Demonstration of antispermatozoal antibodies in varicocele-related infertility with an enzyme-linked immunosorbent assay (ELISA). Fertil Steril. 1986;45(3):397-402. doi:10.1016/s0015-0282(16)49224-1
[65] Falcone M, Bocu K, Keskin H, et al. Anti-sperm Antibody Positivity in Men with Varicocele: A Systematic Review and Meta-Analysis. World J Mens Health. 2025;43(1):60-69. doi:10.5534/wjmh.240003
[66] Bozhedomov VA, Lipatova NA, Rokhlikov IM, Alexeev RA, Ushakova IV, Sukhikh GT. Male fertility and varicocoele: role of immune factors. Andrology. 2014;2(1):51-58. doi:10.1111/j.2047-2927.2013.00160.x
[67] Wang F, Chen R, Jiang Q, et al. Roles of Sialic Acid, AXL, and MER Receptor Tyrosine Kinases in Mumps Virus Infection of Mouse Sertoli and Leydig Cells. Front Microbiol. 2020;11:1292. Published 2020 Jun 29. doi:10.3389/fmicb.2020.01292
[68] Peerayeh SN, Yazdi RS, Zeighami H. Association of Ureaplasma urealyticum infection with varicocele-related infertility. J Infect Dev Ctries. 2008;2(2):116-119. Published 2008 Apr
[69] Colosi HA, Jalali-Zadeh B, Colosi IA, Simon LM, Costache CA. Influence of Toxoplasma gondii Infection on Male Fertility: A Pilot Study on Immunocompetent Human Volunteers. Iran J Parasitol. 2015;10(3):402-409.
[70] Naumenko V, Tyulenev Y, Kurilo L, et al. Detection and quantification of human herpes viruses types 4-6 in sperm samples of patients with fertility disorders and chronic inflammatory urogenital tract diseases. Andrology. 2014;2(5):687-694. doi:10.1111/j.2047-2927.2014.00232.x
[71] Vicari E, Arcoria D, Di Mauro C, Noto R, Noto Z, La Vignera S. Sperm output in patients with primary infertility and hepatitis B or C virus; negative influence of HBV infection during concomitant varicocele. Minerva Med. 2006;97(1):65-77.
[72] Mak TN, Fischer N, Laube B, et al. Propionibacterium acnes host cell tropism contributes to vimentin-mediated invasion and induction of inflammation. Cell Microbiol. 2012;14(11):1720-1733. doi:10.1111/j.1462-5822.2012.01833.x
[73] Türk S, Korrovits P, Punab M, Mändar R. Coryneform bacteria in semen of chronic prostatitis patients. Int J Androl. 2007;30(2):123-128. doi:10.1111/j.1365-2605.2006.00722.x
[74] Perletti G, Magri V. Re: Shoskes et al: The Urinary Microbiome Differs Significantly Between Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls as Well as Between Patients With Different Clinical Phenotypes (Urology 2016 March 9. pii: S0090-4295(16)00267-3. doi: 10.1016/j.urology.2016.02.043). Urology. 2016;94:315-316. doi:10.1016/j.urology.2016.04.028
[75] Ouzounova-Raykova V, Ouzounova I, Mitov IG. May Chlamydia trachomatis be an aetiological agent of chronic prostatic infection?. Andrologia. 2010;42(3):176-181. doi:10.1111/j.1439-0272.2009.00973.x
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Copyright (c) 2025 Mateusz Warzocha, Halszka Wajdowicz, Adrianna Antoszewska, Weronika Bargiel, Dominika Bąk, Julia Buszek, Piotr Czerniak, Michał Medygrał, Małgorzata Dydoń-Pikor
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